Pentadecapeptide BPC 157, in clinical trials as a therapy for inflammatory bowel disease (PL14736), is effective in the healing of colocutaneous fistulas in rats: role of the nitric oxide-system

This 2008 paper in the *Journal of Pharmacological Sciences* examines colocutaneous fistula healing — a colon-to-skin tract that doesn't close on its own — in rats given BPC-157 either parenterally (injected) or perorally (oral). The peptide accelerated fistula closure across macroscopic, microscopic, biomechanical, and functional measurements. The authors then tested whether the effect required intact nitric oxide signaling: blocking NO synthesis (with L-NAME) or potentiating it (with L-arginine) did not abolish BPC-157's healing effect, suggesting the peptide does not act through a single NO-dependent pathway. As comparators, sulfasalazine — the conventional inflammatory bowel disease drug — was only modestly effective, and corticosteroids actively worsened healing. The paper is notable both for the practical finding (oral dosing produced an effect comparable to injection in this model) and for its connection to the human PL 14736 program — the same molecule progressed to Phase II trials in ulcerative colitis under that development code.

The experiments are rat studies, not human. The colocutaneous fistula model is a useful surrogate for one specific complication of inflammatory bowel disease, but it does not by itself establish efficacy for the broader IBD spectrum (mucosal inflammation, remission induction, fistula in Crohn's). The "oral works as well as injection" finding rests on this single rodent model and has not been replicated in humans; oral bioavailability of peptides in human GI tract is generally a much harder problem than in rats. The PL 14736 Phase II human trial referenced in the title was completed but its detailed efficacy results were never published in a peer-reviewed journal. Treat the rat NO-independence finding as a mechanistic clue, and the "human trials are happening" framing as historically accurate but no longer indicative of an active clinical program.